1. Field of the Invention
The present invention relates generally to a method of separating Yttrium-90 (Y-90) from Strontium-90 (Sr-90). Uses of the Y-90 purified by the method include cancer research and treatment, such as for use in cell directed therapy.
2. Description of the Related Art
Radiation therapy (radiotherapy) refers to the treatment of diseases, including primarily the treatment of tumors such as cancer, with radiation. Radiotherapy is used to destroy malignant or unwanted tissue without causing excessive damage to the nearby healthy tissues.
Ionizing radiation can be used to selectively destroy cancerous cells contained within healthy tissue. Malignant cells are normally more sensitive to radiation than healthy cells. Therefore, by applying radiation of the correct amount over the ideal time period, it is possible to destroy all of the undesired cancer cells while saving or minimizing damage to the healthy tissue. For many decades, localized cancer has often been cured by the application of a carefully determined quantity of ionizing radiation during an appropriate period of time. Various methods have been developed for irradiating cancerous tissue while minimizing damage to the nearby healthy tissue. Such methods include the use of high-energy radiation beams from linear accelerators and other devices designed for use in external beam radiotherapy.
Another method of radiotherapy includes cell directed therapy. Here a targeting molecule, which is a binding partner of a molecule on a cancer cell, is radiolabeled. Examples of such targeting molecules include antibodies, e.g., monoclonal antibodies. The targeting molecule may be radiolabeled directly or indirectly via another molecule (e.g., chelating compound) that binds a radionuclide and is attached to the targeting molecule.
Yttrium-90 (Y-90) with a half-life of 64 hours is finding an increasing use in the treatment of various forms of cancer. The National Cancer Institute (NCI) has listed Y-90 as one of the top three radioactive isotopes being evaluated for use in cancer therapy. In fact Y-90 is the cancer-killing isotope used in the first FDA approved radiopharmaceutical used in cell directed therapy, with a specific use for the treatment of non-Hodgkin's Lymphoma. However, Y-90, a beta emitter, has important properties and is expected to be similarly used for many forms of cancer treatment. Medical researchers studying cancer treatment for the past 18 years have developed techniques using radioactive Y-90 labeled monoclonal antibodies to treat the fatal adult T-cell leukemia. Others are using Y-90 labeled antibodies for studies of tumor therapy of ovarian, colon and lymphatic cancers. The appropriate doses of chelate linked antibodies have been prepared and clinical protocols are being readied at major medical institutions such as the National Institute of Health (NIH), Bethesda, Md.; the Oak Ridge Associated Universities, Oak Ridge, Tenn.; and the University of California, Davis Medical Center, Sacramento, Calif.
With the increasing demand for Y-90, there is a need for a method capable of producing multi-curie quantities of Y-90 on a weekly basis. The Y-90 must be chemically and radio chemically pure. Sr-90/NY-90 separation factors less than 1×10−6 (and preferably less than 1×10−8) are required in order to reduce human exposure to long-lived Sr-90. In addition, numerous metal cations (e.g., iron, nickel, zirconium, etc.) interfere with Y-90 binding to monoclonal antibodies and should be reduced to less than 10 ppm (parts per million) per curie of Y-90.
Yttrium-90 is produced by radioactive decay of Sr-90. A primary U.S. source of Y-90 is found in the nuclear fission product waste containing Sr-90, stored in highly radioactive waste tanks at the Hanford nuclear site near Richland, Wash. A representation of the in-growth of Y-90 from 3.5 Ci of Sr-90 as a function of time (assuming the original 3.5 Ci of Sr-90 is void of Y-90) is shown in FIG. 1. It requires between 14 and 21 days to come to equilibrium. To separate the Y-90, the Sr-90 target is “milked” multiple times over selected intervals, such as 14 days in which over 95% of the Y-90 is available, as depicted in FIG. 2. If the “cow” is milked on a 7-day interval (FIG. 3), the amount of available Y-90 drops to ˜75% of the initial “cow” radioactivity. The “milking” interval selected is usually dependent on the demand for Y-90 and the amount of Sr-90 “cow” available.
In order to be useful, the separated Y-90 must be exceptionally pure, free from other metal ions and free from Sr-90, an extremely toxic bone-seeking isotope. The typical therapeutic dose of Y-90 labeled monoclonal antibodies is in the range of 100-300 millicuries of Y-90 per patient. Since an antibody is modified to contain only one molecule of chelating ligand per molecule of immunoprotein within the antibody, the total binding sites for metal ions are limited to about 7×10−9 moles on 1 mg of chelate-modified immunoprotein. Since complexes of several metal ions including zirconium (IV) and iron (III) form much stronger bonds than Y-90, specifications for chemical purity of Y-90 are necessarily strict for efficient labeling.
The Y-90 is formed by the decay of Sr-90 with a 30-year half-life. Y-90 decays with a 68-hour half-life to form non-radioactive zirconium (Zr). Even if the Sr-90 starting feed is free from other metallic impurities, Zr(IV) will continue to build up in the cow and will require separation from the purified Y-90.
There is a need in the art for a method capable of producing multi-curie quantities of chemically and radiochemically pure Y-90 on a weekly basis. Due to the need for highly purified Y-90 and the deficiencies in the current approaches in the art, there is a need for improved methods. The present invention fulfills this need and further provides other related advantages.